Significance The long term objective of this research is to establish a reliable nonhumanprimate model for human papillomavirus (HPV) genital tract infection and disease. Objectives This study investigates 1) the ability to produce clinically apparent HPV tissue changes with more profound immunosuppression; 2) the requirement of SIV-induced immunosuppression; and 3) the utility of this model for evaluating preventative vaccine candidates for genital HPV. Results SIV infected animals have shown histological evidence of papillomavirus infection and immunohistochemical evidence of foci of antigen-bearing cells in the upper layers of the cervical epithelium 4-6 weeks following HPV-11 infection. Rapid, high-titered response to HPV viral antigens following infection appears to correspond to lack of evidence for viral protein synthesis within genital tissues, as determined by immunohistochemical analysis. This type of response was observed in one of SIV -naive animals but not in the SIV-infected animals. Two lavage specimens analyzed by polymerase-chain reaction for the presence of papillomavirus-associated sequence have demonstrated the presence of PCR amplified sequence corresponding to the biopsy specimens positive by immunohistochemistry obtained on the same dates. The animals receiving vaccinations prior to virus inoculation demonstrated serum IgG reactivity by ELISA and HPV-11 neutralizing antibodies by the in vitro infectivity assay. In vaginal secretions collected by lavage, an IgA response was induced in both animals, however only one of the animals developed secretory HPV-11 neutralizing antibodies. The one animal that failed to generate neutralizing antibodies in the lavage was one of the two animals mentioned previously that was positive for viral nucleic acid as well as capsid protein. Current studies are determining the magnitude, quality and duration of the induced response as a prelude to further vaccinations. Future Directions Establish reproductible infection as well as optimization of mucosal vaccination. KEYWORDS human papillomavirus, genital infection, mucosal vaccination